The dementia of Alzheimer's Disease (AD) is caused by the buildup in the brain over many years of amyloid. Therefore, the development of a brain scan that measures brain amyloid could identify those individuals at risk for the later development of AD. Early detection can lead to early therapy and delay the onset of symptoms. It is estimated that the delay of the onset of symptoms of AD, for just 5 years, would save $50 billion per year in U.S. health care costs. The number of people who are potential candidates for an AD diagnostic brain scan is in excess of 30 million in United States alone. The goal of this work is the development of an AIzheimer's Disease (AD) diagnostic brain scan. AD is caused by the deposition of amyloid in the brain and a diagnostic brain scan for AD could be developed if amyloid imaging agents were made transportable through the blood brain barrier (BBB). This work will prepare a genetically engineered fusion protein wherein the amyloid-imaging agent is fused to a targeting ligand that undergoes receptor-mediated transport across the BBB in vivo. This BBB transport vector has been genetically engineered to enable use in humans without immunological reaction. The fusion protein will be a bi-functional molecule that not only crosses the BBB, but also binds to the amyloid plaques of AD brain in vivo, and contains a chelator moiety for radiolabeling. In phase I, the fusion gene was engineered, cell lines were produced, and the bi-funtionality of the fusion protein was demonstrated--the fusion protein both binds the BBB receptor and binds the AD amyloid. The phase II work will produce a cell line secreting the fusion protein, and the production of this protein will be scaled up for manufacturing. Following the validation of the fusion protein, the pharmacology/toxicology and IND preparation will be performed during the 03 year. The completion of the phase II work will enable the preparation of an IND to the FDA for testing of this novel in vivo brain scan that will be the first diagnostic test specific for AD. The AD brain scan may allow for the early detection of those individuals at risk for later development of brain amyloid and AD, and allow for early drug therapy.